Grant Abstract

Abstract: This application proposes a training program to develop Cynthia McEvoy, MD, into an independent clinician-scientist specializing in investigations of pulmonary function testing in neonates and infants. Dr. McEvoy is a board certified Pediatrician with subspecialty training in neonatology. The mentored career development plan consists of a three-tiered approach: a didactic education resulting in a Master in Clinical Research degree, a broad-based experiential learning program, and a mentored clinical research experience. The primary goal will be for Dr. McEvoy to achieve independence as a clinical investigator in all respects. Dr. McEvoy is currently enrolled in the Humans Investigation Program at Oregon Health and Science University (OHSU). This is a two-year K30 (NIH) conducted program for the purposes of developing patient-oriented research skills. Mentored research will be conducted under the direction of a mentorship committee composed of Dr. Cynthia Morris, Professor of Medical Informatics and Outcomes Research, OHSU;Dr. Sonia Buist, Professor of Public Health and Preventive Medicine, OHSU; Dr. Dawn Peters, biostatistician, OHSU; and Dr. Michael Wall, Chief, Division of Pediatric Pulmonology. Dr. Manuel Durand from the University of Southern California will serve as an off-site mentor and committee member. The proposed research is a prospective blinded trial to determine if supplemental Vitamin C given to smoking pregnant women can block the in utero effects of smoking on fetal lung development. About 12% of women smoke during pregnancy with at least 500,000 smoke-exposed babies born per year. These infants have altered pulmonary function at birth with increased respiratory morbidities including increased childhood asthma. We hypothesize that nicotine interacts with nicotinic receptors in the developing lung, causing altered growth and pulmonary function. Some of nicotine's receptor mediated actions need reactive oxygen intermediates and may be blocked by the anti-oxidant Vitamin C. This is supported by data in primates. The primary aim is to establish that supplemental Vitamin C can block the in utero effects of smoking on fetal lung development/pulmonary function measured at birth. A secondary aim is to document that infants delivered to smoking mothers randomized to supplemental Vitamin C during gestation have improved pulmonary function at 12 months of age compared to infants delivered to smoking mothers randomize to placebo during gestation.